The premenstrual syndrome (PMS) is a cyclic disorder occurring during the late luteal phase of the menstrual cycle and ending once menstrual flow returns. The condition was first described over sixty years ago as "premenstrual tension syndrome". The most common symptoms of PMS include bloating, abdominal discomfort, change in appetite, breast tenderness, and headache. Behavioral changes include fatigue, depression, anxiety, irritability, anger, confusion, and social withdrawal.
The symptoms of PMS are often so severe and widespread that the American Psychitric Association has formally identified the diagnostic criteria for PMS in Diagnostic and Statistical Manual of Mental Disorders.
The specific etiology of PMS remains unknown, although many theories have been proposed. These include: hormonal imbalances, hormonal deficiencies, vitamin deficiencies, disturbances of the autonomic nervous system, salt and water imbalances, altered endogenous opiates and psychosomatic dysfunction. Up to now, investigative studies of etiology have been inconclusive and sometimes conflicting. M. Ferin, R. Jewelewicz and M. Warren, The Menstrual Cycle: Physiology, Reproductive Disorders, and Infertility, pp. 198-204 (1993). Most likely, PMS is multifactorial and probably also involves changes in neurohormones and neurotransmitters, which are not easily documented in humans.
Numerous attempts have been made to develop an effective treatment for the symptoms of PMS. Dietary modification including reduction of salt, alcohol, and beverages containing caffeine have been suggested. Pharmacologic intervention is commonly used, especially progesterone therapy and hypothalamic-pituitary-ovarian axis suppressors.
Nonprescription pharmacologic compositions have also been made available. Most provide aspirin or acetaminophen as an analgesic for diminishing menstrual pain. Calcium has also been found to be an effective treatment, especially in regard to premenstrual pain and water retention. S. Thys-Jacobs, S. Ceccarelli, A. Bierman, H. Weisman, M. A. Cohen and J. Alvir, Calcium supplementation in premenstrual syndrome: A randomized crossover trial, J. Gen. Int. Med. 4:183-189,(1989). Magnesium supplementation has been documented to relieve certain other symptoms of PMS including pain, negative affect and arousal i.e. mood fluctuations although other symptoms were unaffected. F. Fancchinetti, P. Borella, G. Sances, L. Fioroni, R. Nappi and A. R. Genazzani, Oral Magnesium Successfully Relieves Premenstrual Mood Changes, Obstetrics & Gynecology 78:177-181,(1991).
None of the prior art nonprescription compositions have been found to be completely effective. Although they alleviate certain symptoms of PMS, other symptoms remain untreated or show little or no improvement. Further, at least some prior art compositions are known to contain ingredients that cause undesirable side effects. For example, U.S. Pat. No. 5,001,688 (Calam et al.) contains both ethyl alcohol and an antihistamine which can cause drowsiness. Further, none of the active ingredients reduce negative effect, fatigue or bloating. Midol, a commercially available nonprescription composition has contained aspirin along with caffeine and an antispasmodic ingredient. Recent investigations have indicated that consumption of caffeine containing beverages is strongly related to the prevalence and severity of PMS and should therefore be avoided. A. Mackay--Rossignol and H. Bonnlander, Caffeine-Containing Beverages, Total Fluid Consumption., and Premenstrual Syndrome, Am. J. Pub. Health, pg.1106 (1990).
Thus, a patient is often left with no other choice than to simultaneously take different compositions in an attempt to relieve all of the various symptoms while at the same time try to avoid those known to produce side effects. For obvious reasons such self-medication is undesirable. Even the relatively benign ingredients found in nonprescription drugs present the potential for an overdose. Further, interaction between active ingredients found in different compositions can actually reduce the overall effectiveness of treatment, especially if the active ingredients operate by a similar mechanism.
Since PMS encompasses a broad spectrum of symptomatology, physicians are faced with a variety of options when deciding on a safe program of treatment. A need has therefore arisen for a single nonprescription composition that will provide a broad therapeutic spectrum while exhibiting greater overall activity.
Against this background the present invention was developed.